While the virtually identical phenotypes of the Pcdhgtcko/tcko and Pcdhgdel/del mutants demonstrate that C-type isoforms are essential, it is also possible that the entire repertoire of Pcdhg genes are required; that is, each isoform is indispensable. Indeed, essentially every Pcdhg gene in humans has an ortholog in the mouse, in contrast to the Pcdha and Pcdhb genes (Wu et al., 2001). To address this possibility, we deleted Pcdhga1, Pcdhga2 and Pcdhga3 genes in the mouse (Figures 1A–B and S1B). The triple A-type isoform knockout (TAKO) mutants are viable and fertile, and survive to adulthood with no discernible abnormalities (Figure 1E and Movie S1).
